Cost-effectiveness of second-line vasopressors for the treatment of septic shock.

PURPOSE: To determine the cost-effectiveness of escalating doses of norepinephrine or norepinephrine plus the adjunctive use of vasopressin or angiotensin II as a second-line vasopressor for septic shock. MATERIALS AND METHODS: Decision tree analysis was performed to compare costs and outcomes associated with norepinephrine monotherapy or the two adjunctive second-line vasopressors. Short- and long-term outcomes modeled included ICU survival and lifetime quality-adjusted-life-years (QALY) gained. Costs were modeled from a payer's perspective, with a willingness-to-pay threshold set at $100,000/unit gained. One-way (tornado diagrams) and probabilistic sensitivity analyses were performed. RESULTS: Adjunctive vasopressin was the most cost-effective therapy, and dominated both norepinephrine monotherapy and adjunctive angiotensin II by producing higher ICU survival at less cost. For the lifetime horizon, while norepinephrine monotherapy was least expensive, adjunctive vasopressin was the most cost-effective with an incremental cost-effectiveness ratio of $19,762 / QALY gained. Although adjunctive angiotensin II produced more QALYs compared to norepinephrine monotherapy, it was dominated in the long-term evaluation by second-line vasopressin. Sensitivity analyses demonstrated model robustness and medication costs were not significant drivers of model results. CONCLUSIONS: Vasopressin is the most cost-effective second-line vasopressor in both the short- and long-term evaluations. Vasopressor price is a minor contributor to overall cost.

Mortality, Morbidity, and Costs After Implementation of a Vasopressin Guideline in Medical Intensive Care Patients With Septic Shock: An Interrupted Time Series Analysis.

Background: Vasopressin decreases vasopressor requirements in patients with septic shock. However, the optimal norepinephrine dose for initiation or cessation of vasopressin is unclear. Objective: Analyze monthly intensive care unit (ICU) mortality rates 1 year preimplementation and postimplementation of a guideline suggesting a norepinephrine dose of 50 µg/min or more for initiation of vasopressin and early cessation of vasopressin. Methods: This retrospective quasi-experimental study included adult patients with septic shock admitted to the medical ICU of a tertiary care medical center over 2 years. Time periods were evaluated with interrupted time series analysis. Results: A total of 1148 patients were included: 573 patients preguideline and 575 patients postguideline. Group characteristics were well balanced at baseline, except patients postguideline had higher sequential organ failure assessment scores. Postguideline, fewer patients were initiated on vasopressin (305 [53.2%] vs 217 [37.7%], absolute difference -15.5% [95% CI -21.2% to -9.8%]), and the norepinephrine dose at vasopressin initiation was higher (median 25 [interquartile range 18, 40] µg/min vs 40 [22, 52] µg/min; median difference 15 [95% CI 11 to 19] µg/min; P < 0.01). After guideline implementation, there was no evidence for a difference in ICU mortality rate slope (slope change 0.07% [95% CI -0.8% to 1.0%] per month; P 0.87), but the vasoactive cost level decreased by US$183 (95% CI -US$327 to -US$39) per patient immediately after implementation. Conclusion and Relevance: Implementation of a guideline suggesting a high norepinephrine dose threshold for vasopressin initiation and early vasopressin cessation in patients with septic shock appears to be safe and may decrease vasoactive costs.

Delayed vasopressor initiation is associated with increased mortality in patients with septic shock.

PURPOSE: Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes. MATERIALS AND METHODS: This retrospective, single-centered, cohort study included patients with septic shock from January 2017 to July 2017. Time from initial hypotension to vasopressor initiation was measured for each patient. The primary outcome was 30-day mortality. RESULTS: Of 530 patients screened,119 patients were included. There were no differences in baseline patient characteristics. Thirty-day mortality was higher in patients who received vasopressors after 6 h (51.1% vs 25%, p < .01). Patients who received vasopressors within the first 6 h had more vasopressor-free hours at 72 h (34.5 h vs 13.1, p = .03) and shorter time to MAP of 65 mmHg (1.5 h vs 3.0, p < .01). CONCLUSION: Vasopressor initiation after 6 h from shock recognition is associated with a significant increase in 30-day mortality. Vasopressor administration within 6 h was associated with shorter time to achievement of MAP goals and higher vasopressor-free hours within the first 72 h.

Efectividad y seguridad de somatostatina comparada con octreotida y terlipresina para el control de la hemorragia de vías digestivas altas en adultos con várices esofágicas / Effectiveness and safety of somatostatin compared to octreotide and terlipressin for the control of upper gastrointestinal tract bleeding in adults with esophageal varices

Antecedentes: Descripción de la condición de salud de interés: La hipertensión portal, es comúnmente causada por la cirrosis hepática, resulta en varios flujos venosos colaterales por los cuales la sangre del sistema porta alcanza la circulación sistémica. De éstos flujos colaterales los que son clínicamente significativos son aquellos que circundan el cardias, donde la vena gástrica izquierda, la vena gástrica posterior y las venas gástricas cortas eventualmente se anastomosan con la vena ácigos menor y con la vena intercostal del sistema venoso sistémico. Esto lleva a la formación de alteraciones en la capa submucosa del tercio inferior del esófago y del fondo del estómago, y se denominan comúnmente várices. La importancia clínica radica en que la ruptura de estas várices resulta en una hemorragia gastroesofágica que es la complicación letal más frecuente de la cirrosis. Descripción de la tecnología: La somatostatina es una hormona del grupo de las hormonas hipofisiarias. La siguiente es la descripción del grupo H "Hormonas sistémicas excluyendo las hormonas sexuales y las insulinas" al cual pertenece. Evaluación de efectividad y seguridad: Pregunta de investigación: La pregunta de investigación fue validada teniendo en cuenta las siguientes fuentes de información: registro sanitario INVIMA, Acuerdo 029 de 2011, guías de práctica clínica, reportes de evaluación de tecnologías, revisiones sistemáticas y narrativas de la literatura, estudios de prevalencia/incidencia y carga de enfermedad, consulta con expertos temáticos, y otros actores clave. \r\nNo se identificaron otros comparadores relevantes para la evaluación. Población: Adultos con hemorragia de vías digestivas altas secundaria a várices esofágicas. Metodología: Búsqueda de literatura, Búsque\r\nda en bases de datos electrónicas. Conclusiones: -Efectividad: somatostatina, octreotide y terlipresina\r\nson efectivas para el tratamiento de pacientes adultos con hemorragia de vías digestivas altas secundaria a várices esofágicas. No hay diferencias estadísticamente significativas entre ellas al evaluar mortalidad, control \r\ndel sangrado y resangrado; -Seguridad: En el estudio incluido no se encontraron datos acerca de la ocurrencia de eventos adversos entre somatostatina y sus comparadores.

A human vascular model based on microdialysis for the assessment of the vasoconstrictive dose-response effects of norepinephrine and vasopressin in skin.

OBJECTIVE: Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin. METHODS: We investigated whether increasing concentrations of norepinephrine (NE, 1.8-59 µmol/L) and vasopressin (VP, 1-100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate). RESULTS: We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose response model. Urea in the dialysate increased from a baseline of 7.9 ± 1.7 to 10.9 ± 0.9 mmol/L for the highest concentration of NE (p < 0.001) and from 8.1 ± 1.4 to 10.0 ± 1.7 mmol/L for the highest concentration of VP (p = 0.037). Glucose decreased from 2.3 ± 0.7 to 0.41 ± 0.18 mmol/L for NE (p = 0.001) and from 2.7 ± 0.6 to 1.3 ± 0.5 mmol/L for VP (p < 0.001). Lactate increased from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for NE (p = 0.005) and from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for VP (p = 0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters. CONCLUSIONS: Microdialysis in the skin, either with a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects.

[Assessment of different homeostatic methods used in laparoscopic intramural myomectomy].

OBJECTIVE: To explore the safe and effective method of hemostasis in laparoscopic hysteromyomectomy (LM). METHODS: Two hundred and eighty women with symptomatic uterine intramural fibroids undergoing LM were assigned to 4 groups, Group A undergoing fibroid pedicle ligation, Group B injected with 12 IU diluted vasopressin around the myoma, Group C injected with 20 IU oxytocin combined with pedicle ligation, and Group D injected with vasopressin combined with pedicle ligation. The operation time, amount of blood loss, operative complications, bowel deflation, post-operative hemoglobin dropping, and length of hospital stay were compared. RESULTS: The amounts of blood loss of Groups A and C were (171 +/- 146) ml and (184 +/- 140) ml, both significantly higher than those of Groups B and D [(115 +/- 70) ml and (106 +/- 73) ml, both P < 0.01]. The length of hospital stay of Group D was (2.9 +/- 0.5) d, significantly shorter than those of Groups A, B, and C [(3.1 +/- 0.7) d, (3.6 +/- 0.8) d, and (3.3 +/- 0.7) d, all P < 0.05]. The bowel deflation time of Group D was (20 +/- 6) h, significantly shorter than those of the Groups A, B, and C [(26 +/-) h, (25 +/- 7) h, and (25 +/- 8) h respectively, all P < 0.05]. The post-operative hemoglobin dropping of group D was (1.1 +/- 0.9) g/L, significantly less than those of Groups A, B, and C [(1.5 +/- 1.0), (1.4 +/- 0.8), and (1.2 +/- 0.7) g/L respectively, all P < 0.05]. CONCLUSIONS: Vasopressin (12 IU) injection around the myoma is a simple, effective, and safe homeostatic procedure during LM. Pedicle ligation can reduce advanced post-operative bleeding post-operation.

Vasopressin in vasodilatory shock: hemodynamic stabilization at the cost of the liver and the kidney?

Infusing arginine vasopressin (AVP) in advanced vasodilatory shock is usually accompanied by a decrease in cardiac index and systemic oxygen transport. Whether or not such a vasoconstriction impedes regional blood flow and thus visceral organ function, even when low AVP is used, is still a matter of debate. Krejci and colleagues now report, in this issue of Critical Care, that infusing 'low-dose' AVP during early, short-term, normotensive and normodynamic fecal peritonitis-induced porcine septicemia markedly reduced both renal and portal blood flow, and consequently total hepatic blood flow, whereas hepatic arterial flow was not affected. This macrocirculatory response was concomitant with reduced kidney microcirculatory perfusion, whereas liver micro-circulation remained unchanged. From these findings the authors conclude that the use of AVP to treat hypotension should be cautioned against in patients with septic shock. Undoubtedly, given its powerful vasoconstrictor properties, which are not accompanied by positive inotropic qualities (in contrast with most of the equally potent standard care 'competitors', namely catecholamines), the safety of AVP is still a matter of concern. Nevertheless, the findings reported by Krejci and colleagues need to be discussed in the context of the model design, the timing and dosing of AVP as well as the complex interaction between visceral organ perfusion and function.